Research On 22q11.2 Microdeletion In Patients With Cono-truncal Deformanity

Partâ… Determining the frequency of 22qll.2 microdeletions in Chinese pediatric patients with conotruncal defect by fluorescence in-situ hybridizationObjectiveTo determine the frequency of 22qll.2 microdeletions in Chinese pediatric patients with conotruncal defect.MethodsA total of 65 Chinese pediatric conotruncal heart defect patients(27 with tetralogy of fallot,13 with double outlet right ventricle,2 with pulmonary artery atresia with ventricular septal defect,2 with corrected transposition of the great arteries,3 with transposition of the great arteries,1 with double outlet left ventricle,3 with persistent truncus arteriosus,2 with aortic stenosis,1 with aortic stenosis associated with aortic insufficiency,9 with pulmonary stenosis and 2 with aortic coarctation),22 females and 43 male ranging in age from 0.03 to 11 years, were included in our study.We did dural-color bacterial artificial chromosome fluorescence in situ hybridization with RP11-316L10/CTD-2335H16 probe to find the chromosome 22qll.2 deletion in peripheral blood cells of patients.ResultsChromosome 22qll.2 microdeletion was detected in 5(5/65)patients with conotruncal defects.The total frenquency of 22qll.2 deletion was 7.7%. 7.4%in TOF,15.4%in DORV,33.3%in persistent truncus arteriosus.There was no 22qll.2 deletion detected in patients with PA,or TGA,or PS,or AS,or AS associated with AI,or aortic coarctation,or DOLV.ConclusionThe frequency of 22qll.2 deletion was 7.7%in the group of patients with conotruncal defects.The results indicated that microdeletion of 22qll.2 is an important genetic etiology in patients with some category of conotruncal defects.Partâ…¡Study of the genetic mechanism of 22qll.2 microdeletion syndromeObjectiveTo study the genetic mechanism of 22qll.2 microdeletion syndrome in Chinese pediatric patients with conotruncal defect.MethodsThe directive relatives of the positive patients were included in our study.We did dural-color bacterial artificial chromosome fluorescence in-situ hybridization with RP11-316L10/CTD-2335H16 probe to find the chromosome 22qll.2 deletion in peripheral blood cells of the directive relatives of the positive patients.To determine the length of 22qll.2 deletion,the parental origin of the deleted chromosome,and relation of genotype to phenotypes,using fluorescence-based semi-automate gene scan and gene typing with 20 polymorphic short tandem repeats(STR) markers:D22S420,D22S427,D22S1569,D22S1571,D22S1646,D22S1648, D22S941,D22S1622,D22S1644,D22S944,D22S1627,D22S264,D22S934, D22S1201,D22S1018E,D22S555,D22S935,D22S1709,D22S939,D22S308 in chromosome 22qll.2 region.Genomic DNA was isolated from peripheral blood leukocytes.PCR was used to analyze the 20 STR markers.The amplified fragments were analyzed with Genescan 3.0 and Genetyper 2.1. To define the deletion at the individual patient level,we conducted detailed haplotype analysis on 5 patients and their directive relatives.And the haplotypes of parents were deduced from the genotype of the patient.ResultsWe found a Chinese family with recurrence of 22qll.2 deletion detected by standard FISH tests.In this family,the affected progenitor of the index patient with PTA(typeâ…£)was his mother.20 highly polymorphic microsatellite repeat markers from within 22qll.2 were used to determine the size of the deleted region and the parental origin of the deletions of the index patient,his affected mother and other affected patients.The the parental origin of the deleted chromosome in our 6 positive patients were all maternal.There is no correlation between the phenotype and size of 22q11.2 deletions.ConclusionMost 22q11.2 deletions occur as de novo lesions,only a small number of patients inherited from an affected parent.There is no correlation between the phenotype and size of 22q11.2 deletions.There was a preponderance of maternally derived deletions in our study.